Characterization of a novel protein-binding module - the WW domain

Marius Sudol, Henry I. Chen, Cecile Bougeret, Aaron Einbond, Peer Bork

Research output: Contribution to journalShort surveypeer-review

295 Scopus citations

Abstract

We have identified, characterized and cloned human, mouse and chicken cDNA of a novel protein that binds to the Src homology domain 3 (SH3) of the Yes proto-oncogene product. We subsequently named it YAP for Yes-associated protein. Analysis of the YAP sequence revealed a protein module that was found in various structural, regulatory and signaling molecules. Because one of the prominent features of this sequence motif is the presence of two conserved tryptophans (W), we named it the WW domain. Using a functional screen of a cDNA expression library, we have identified two putative ligands of the WW domain of YAP which we named WBP-1 and WBP-2. Peptide sequence comparison between the two partial clones revealed a homologous proline-rich region. Binding assays and site-specific mutagenesis have shown that the proline-rich motif binds with relatively high affinity and specificity to the WW domain of YAP, with a preliminary consensus that is different from the SH3-binding PXXP motif. This suggests that the WW domain has a role in mediating protein-protein interactions via proline-rich regions, similar but distinct from Src homology 3 (SH3) domains. Based on this finding, we hypothesize that additional protein modules exist and that they could be isolated using proline-rich peptides as functional probes.

Original languageEnglish
Pages (from-to)67-71
Number of pages5
JournalFEBS Letters
Volume369
Issue number1
DOIs
StatePublished - 1 Aug 1995
Externally publishedYes

Keywords

  • Polyproline
  • Protein module
  • Protein-protein interaction

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